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A Cross-Tissue Transcriptome Association Study Revealed Novel Susceptibility Genes for Chronic Obstructive Pulmonary

Hao Luan1, Tianhua Wang2, Xinjie Su3

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International Journal of Chronic Obstructive Pulmonary Disease
|March 13, 2026
PubMed
Summary

Researchers identified two new genes, DNAJA4 and IREB2, causally linked to chronic obstructive pulmonary disease (COPD). This discovery offers a fresh perspective on the genetic underpinnings of COPD, advancing our understanding of the disease.

Keywords:
COPDcross-tissue TWASsingle-cell transcriptomicssusceptibility gene

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Area of Science:

  • Genetics and Genomics
  • Pulmonary Medicine
  • Bioinformatics

Background:

  • Chronic obstructive pulmonary disease (COPD) is defined by persistent airflow limitation, but its underlying pathogenesis is not fully understood.
  • Genetic factors are increasingly recognized as significant contributors to the development of COPD.

Purpose of the Study:

  • To identify novel predisposition genes for COPD using advanced genetic analysis techniques.
  • To elucidate potential molecular mechanisms underlying COPD pathogenesis.
  • To validate the role of identified genes in COPD development and progression.

Main Methods:

  • Employed transcriptome-wide association studies (TWAS) and single-cell transcriptome analysis.
  • Utilized cross-tissue TWAS with FinnGen R10 and GTEx v8 data, followed by single-tissue/cell validations.
  • Conducted SMR, colocalization, mouse/cell exposure experiments, and GeneMANIA analysis for functional insights.

Main Results:

  • Identified 125 COPD susceptibility genes via cross-tissue TWAS.
  • Discovered and validated two novel COPD susceptibility genes: DNAJA4 and IREB2.
  • DNAJA4 and IREB2 showed specific cell type enrichment in lung tissue and are linked to protein folding and metabolic processes, respectively.

Conclusions:

  • DNAJA4 and IREB2 are novel susceptibility genes causally associated with COPD.
  • These findings offer a new genetic perspective on COPD pathogenesis.
  • Further research into these genes may reveal new therapeutic targets for COPD.